Glia Maturation Factor (GMF) is a protein factor endogenous to the adult brain, which is capable of promoting the growth and differentiation of glioblasts in culture. The factor was first detected in our laboratory and has been partially purified and characterized by us. In this application we propose to study the chemical effects of GMF on monolayer cultures of glioblasts. The following chemical markers will be determined: two universal second messengers, cyclic AMP and cyclic GMP; one general glial marker, the S-100 protein; one astrocytic marker, the GFA protein; one oligodendrocyte marker, 2'3'-cyclic nucleotide-3'-phosphohydrolase; and one neuronal marker, the 14-3-2 protein. We also wish to study the effect of cell aggregation on the spontaneous differentiation (in the absence of GMF) of glioblasts, using the same chemical parameters indicated above. The third part of our study consists of extracting endogenous GMF activity from the monolayer and aggregated glioblasts. The purpose of these experiments is to substantiate our hypothesis that GMF is produced by the glioblasts during the course of development, and that GMF is a cell surface protein which serves as a mediator of intracellular communication when the cells are in maximal physical contact (as in aggregate cultures) but not when they are dispersed or in minimal contact (as in monolayer cultures). Even though GMF may be present in the monolayer cells, the geometric relationship between the factor and the receptors on the same cell prevents self-induction from taking place; the addition of exogenous GMF to the monolayer culture would partially reconstitute the biological environment enjoyed by cells in an aggregate culture.